We have developed methods of purifying leucocyte pyrogen from rabbit peritoneal exudate cells and have raised an antibody to it in goats. This antibody neutralizes the biological effect of both rabbit leukocyte pyrogen and rabbit macrophage pyrogen. We have also prepared pure leukocyte pyrogen lightly iodinated with 125I. We now wish: (1) To obtain more heavily iodinated pyrogen using the succinimide ester technique. (2) To develop high titer anti-leukocyte pyrogen antibody. (3) To develop a radioimmunoassay which can measure pyrogen content in the supernates of cells incubated in vitro and in body fluids. (4) To investigate whether 125I labelled pyrogen binds to hypothalamic neurons. (5) To use the antibody to locate pyrogen precursors within cells. (6) To see whether purified pyrogen has other biological actions besides causing fever. (7) To see if pyrogen, induced by exposing neutrophils to myxoviruses and to antigen-antibody complexes, is identical with that induced by endotoxin. (8) To determine the primary structure of leukocyte pyrogen and see whether the known molecular weight can be completely accounted for by amino acids. To split the molecule with cyanogen bromide and see if one fragment carries the biological activity. (9) To establish whether macrophage pyrogens are synthesized de novo from amino acid precursors.